Breast cancer is a global problem that accounts for nearly a quarter of all cancers in women. Recent studies implicated expression of cyclooxygenase-2 as a marker to identify precursor cells for breast cancer. The purpose of the present work is to investigate the association of genotypic polymorphisms in cyclooxygenase-2 and selenium with breast cancer. Methods: investigation of genotypic polymorphisms of cyclooxygenase-2, measurement of selenium by electrothermal atomic absorption spectrometry (ET-AAS) and investigation of calcium and alkaline phosphatase spectrophotometry in 500 patients with breast cancer and 100 healthy controls from Zagazig University Hospital in Egypt. The results showed significant differences in distribution between the breast cancer and controls. We found 169G allele carriers had a higher risk of breast cancer and results also showed significant decrease in Se and Ca and significant increase in Alk. In conclusion: the G allele of COX-2 gene may be a good marker in breast cancer and evaluation of serum Se, Ca and AlP give a red light in early detection of breast cancer.